Impact of Baseline Central Retinal Thickness on Outcomes in the VIVID-DME and VISTA-DME Studies.
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ABSTRACT:
SUBMITTER: Midena E
PROVIDER: S-EPMC5896224 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Publications
Impact of Baseline Central Retinal Thickness on Outcomes in the VIVID-DME and VISTA-DME Studies.
Midena Edoardo E Gillies Mark M Katz Todd A TA Metzig Carola C Lu Chengxing C Ogura Yuichiro Y
Journal of ophthalmology 20180329
<h4>Purpose</h4>To report the impact of baseline central retinal thickness (CRT) on outcomes in patients with diabetic macular edema (DME) in VIVID-DME and VISTA-DME.<h4>Methods</h4>Post hoc analyses of two randomized controlled trials in which 862 DME patients were randomized 1 : 1 : 1 to treatment with intravitreal aflibercept 2.0 mg every 4 weeks (2q4), intravitreal aflibercept 2.0 mg every 8 weeks after five initial monthly doses (2q8), or macular laser photocoagulation at baseline and as ne ...[more]
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Project description:BACKGROUND/AIMS:To evaluate intravitreal aflibercept versus laser in subgroups of patients with baseline Diabetic Retinopathy Severity Scale (DRSS) scores ≤43, 47, and ≥53 in VIVID-DME and VISTA-DME. METHODS:Patients with diabetic macular oedema were randomised to receive intravitreal aflibercept 2 mg every 4 weeks (2q4), intravitreal aflibercept 2 mg every 8 weeks after five initial monthly doses (2q8), or macular laser photocoagulation at baseline with sham injections at every visit. These post hoc analyses evaluate outcomes based on baseline DRSS scores in patients in the integrated dataset. The 2q4 and 2q8 treatment groups were also pooled. RESULTS:748 patients had a baseline DRSS score based on fundus photographs (≤43, n=301; 47, n=153; ≥53, n=294). At week 100, the least squares mean difference between treatment groups (effect of intravitreal aflibercept above that of laser, adjusting for baseline best-corrected visual acuity) was 8.9 (95% CI 5.99 to 11.81), 9.7 (95% CI 5.54 to 13.91), and 11.0 (95% CI 7.96 to 14.1) letters in those with baseline DRSS scores ≤43, 47, and ≥53, respectively. The proportions of patients with ≥2 step DRSS score improvement were greater in the intravitreal aflibercept group versus laser, respectively, for those with baseline DRSS scores of ≤43 (13% vs 5.9%), 47 (25.8% vs 4.5%), and ≥53 (64.5% vs 28.4%). CONCLUSIONS:Regardless of baseline DRSS score, functional outcomes were superior in intravitreal aflibercept-treated patients, demonstrating consistent treatment benefit across various baseline levels of retinopathy. TRIAL REGISTRATION NUMBERS:NCT01331681 and NCT01363440, Post-results.
| S-EPMC6047149 | biostudies-literature
Project description:BACKGROUND:Diabetic macular edema (DME) shows a gradual and sustained functional and morphologic response to anti-vascular endothelial growth factor (VEGF) drugs, but the optimal schedule for initiation of anti-VEGF therapy is not known. This study evaluates the treatment response behavior of DME in the Phase 3 trials of intravitreal aflibercept, with 5 initial intravitreal aflibercept injections (IAI), 2 mg every 4 weeks (2q4), in the upload phase. METHODS:This post hoc pooled analysis of the VISTA-DME (NCT01363440) and VIVID-DME (NCT01331681) trials evaluated the change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) during the upload phase, using pooled data from both IAI treatment groups [2q4 and 2 mg every 8 weeks (2q8)]. The mean visit-to-visit change in BCVA and CRT, and the respective rate of gainers and losers was calculated for each successive visit. A secondary analysis compared the visit-to-visit change in BCVA between the 2q4 and 2q8 treatment arms during the upload period and the first year treatment period. RESULTS:The majority of eyes showed a continuing improvement of BCVA after the first IAI. The proportions of eyes gaining BCVA (?5 letters) at each visit compared with the previous visit during the IAI 2q4 upload phase were 60 (4-weeks), 19 (8-weeks), 16 (12-weeks), 15 (16-weeks), and 14 % (20-weeks). In contrast, the proportions of eyes losing BCVA (?5 letters) were 3 (4-weeks), 7 (8-weeks), 7 (12-weeks), 9 (16-weeks), and 8 % (20-weeks), respectively. The odds of BCVA (?5 letters) gain/loss exceeded 1.7 at each visit (range 1.7-20). Overall, the proportion of patients with BCVA gain ?5 letters at week 20 (compared with baseline) was 76 and 80 % in the 2q4 and 2q8 groups, respectively. The proportions of eyes showing a visit-to-visit decrease in CRT of ?30 µm during the first 5 IAI were 77 (4-weeks), 27 (8-weeks), 21 (12-weeks), 17 (16-weeks), and 12 % (20-weeks). In the secondary analysis, the BCVA outcomes were similar for the 2q8 and 2q4 treatment arms. CONCLUSIONS:The data presented here are consistent with continual functional and anatomic improvement following the fourth and fifth initial 2q4 injections, suggesting that an intensive and sufficiently long upload may be beneficial. Trial registration VIVID-DME: Clinicaltrials.gov: NCT01331681; VISTA-DME: Clinicaltrials.gov: NCT01363440.
| S-EPMC5088462 | biostudies-literature
Project description:ImportanceMacular edema (ME) is the leading cause of decreased visual acuity (VA) associated with retinal vein occlusion (RVO). Identifying factors associated with better outcomes in RVO eyes treated with anti-vascular endothelial growth factor (VEGF) therapy may provide information useful in counseling patients.ObjectiveTo investigate baseline characteristics associated with 6-month VA and central subfield thickness (CST) outcomes in participants in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2).Design, setting, and participantsA total of 362 patients with central RVO or hemi-RVO were enrolled between September 17, 2014, and November 18, 2015, and randomized 1:1 in a masked fashion to receive bevacizumab or aflibercept. At month 6, 348 participants (96%) had VA outcomes measured and 335 participants (93%) had spectral domain optical coherence tomography outcomes measured. The current data analysis was conducted from February 27, 2017, to April 7, 2017.InterventionsEyes were randomly assigned to receive an intravitreal injection of bevacizumab, 1.25 mg, or aflibercept, 2.0 mg, at baseline and every 4 weeks, with the primary outcome measured at 6 months.Main outcomes and measuresChange from baseline in VA letter score (VALS), VALS gain of 15 or more, change from baseline in CST, CST less than 300 µm, and resolution of ME. Baseline factors associated with 6-month outcome at the 0.05 level in univariate regressions were included in multivariate regressions, with those significant after multiplicity control by the Hochberg method reported.ResultsThe mean (SD) age of patients was 69 (12) years, and 43% were women. Younger patient age (odds ratio [OR], 0.95 per year of age; 95% CI, 0.93-0.98; P = .007) and lower baseline VALS (OR, 0.96 per letter; 95% CI, 0.94-0.98; P < .001) were associated with a 6-month VALS gain of 15 or greater. Compared with bevacizumab, aflibercept treatment was associated with a higher odds of ME resolution (OR, 3.59; 95% CI, 2.22-5.80; P < .001) and CST less than 300 µm (OR, 5.30; 95% CI, 2.40-11.67; P = .001), but not with a better VA outcome. Macular edema was less likely to resolve in eyes that received anti-VEGF treatment prior to study participation (OR, 0.33; 95% CI, 0.17-0.64; P = .03).Conclusions and relevanceIn eyes treated with bevacizumab or aflibercept, younger age and worse baseline VALS were associated with better 6-month VA outcomes. Aflibercept treatment was associated with more favorable spectral domain optical coherence tomography outcomes but not VA outcomes. These findings may be useful in assessing expected response at month 6 after monthly injection of anti-VEGF agents for treating ME due to CRVO and HRVO.Trial registrationclinicaltrials.gov Identifier: NCT01969708.
| S-EPMC5710260 | biostudies-literature
Project description:PURPOSE: To investigate the relationship between retinal sensitivity (RS) assessed by microperimetry (MP) and retinal structural changes in patients with resolved central serous chorioretinopathy (CSC). METHODS: Spectral domain optical coherence tomography (OCT) examination and MP tests were performed in patients with resolved CSC. Point-to-point correlation was performed between RS and corresponding retinal structural changes using Pearson's correlation analysis. In addition, in a 1-mm zone in the central fovea, a correlation was calculated between the mean RS and the mean central retinal thickness (CRT). RESULTS: Eighty-four eyes were analyzed. The total number of MP test points was 1092 (84 eyes × 13 points). The mean RS and retinal point thickness (RPT) of all test points were 13.53±3.84 dB and 208.6±48.0 μm, respectively. The RS and RPT were significantly decreased in the test points with loss of the ellipsoid portion of the inner segments (EPIS) (P<0.0001). Within the 1-mm foveal center zone, there was a significant correlation between mean RS and mean CRT (r=0.432, P<0.0001) and between RS and the corresponding RPT (r=0.339, P<0.0001). CONCLUSION: RS was dependent on the status of the EPIS in patients with resolved CSC. The correlation between mean RS and mean CRT was compatible with the point-to-point correlation between RS and the corresponding RPT.
| S-EPMC4194344 | biostudies-other
Project description:PurposeThis work aimed to assess the incidence of proliferative diabetic retinopathy (PDR) events and improvement to mild non-PDR (NPDR) or better after intravitreal aflibercept injection (IAI) or laser treatment (control) in diabetic macular edema (DME).MethodsPDR events in the VISTA (NCT01363440) and VIVID (NCT01331681) phase 3 clinical trials were evaluated in a combined IAI-treated group (IAI 2 mg every 4 weeks or 2 mg every 8 weeks after 5 initial monthly doses; n = 475) and a macular laser control group (n = 235) through week 100 in eyes without PDR at baseline (Diabetic Retinopathy Severity Scale [DRSS] score ≤ 53). Improvement in the DRSS score to 35 or better was evaluated in those with a baseline DRSS score of 43 or greater.ResultsA lower proportion of eyes in the IAI group than in the laser group developed a PDR event through week 100 (4.4% vs 11.1%; adjusted difference, -6.7%; 97.5% CI, -11.7 to -1.6; nominal P = .0008). All PDR events occurred in eyes with a baseline DRSS score of 43, 47, or 53 and not in those with a score of 35 or less. A greater proportion of eyes in the IAI group than in the control group achieved a DRSS score of 35 or less (20.0% vs 3.8%; nominal P < .0001).ConclusionsFewer eyes with NPDR and DME treated with IAI than eyes treated with a laser had a PDR event. More eyes treated with IAI improved to mild NPDR or better (DRSS score ≤ 35) through 100 weeks.
| S-EPMC9976032 | biostudies-literature
Project description:Radiogenic strontium isotopes (87Sr/86Sr) have long been used in analyses of paleomobility within Mesoamerica. While considerable effort has been expended developing 87Sr/86Sr baseline values across the Maya region, work in central Mexico is primarily focused on the Classic period urban center of Teotihuacan. This study adds to this important dataset by presenting bioavailable 87Sr/86Sr values across central Mexico focusing on the Basin of Mexico. This study therefore serves to expand the utility of strontium isotopes across a wider geographic region. A total of 63 plant and water samples were collected from 13 central Mexican sites and analyzed for 87Sr/86Sr on a Thermo-Finnigan Neptune multi-collector inductively coupled plasma mass spectrometer (MC-ICP-MS). These data were analyzed alongside 16 published 87Sr/86Sr values from two additional sites within the region of interest. A five-cluster k-means model was then generated to determine which regions of the Basin of Mexico and greater central Mexico can and cannot be distinguished isotopically using 87Sr/86Sr values. Although the two clusters falling within the Basin of Mexico overlap in their local 87Sr/86Sr ranges, many locations within the Basin are distinguishable using 87Sr/86Sr values at the site-level. This study contributes to paleomobility studies within central Mexico by expanding knowledge of strontium isotope variability within the region, ultimately allowing researchers to detect intra-regional residential mobility and gain a greater understanding of the sociopolitical interactions between the Basin of Mexico and supporting outlying regions of central Mexico.
| S-EPMC7039465 | biostudies-literature
Project description:Idiopathic epiretinal membrane (iERM) is a pathological fibrocellular change in the vitreoretinal junction over the macular area; however, possible pathogenic mechanisms remain unclear. Changes in the differential protein composition of the aqueous humor (AH) may represent potential molecular changes associated with iERM. To gain new insights into the molecular mechanisms of iERM pathology, a sensitive label-free proteomics analysis was performed to compare AH protein expressions in patients with cataracts with or without iERM. This study employed nanoflow ultra-high-performance liquid chromatography-tandem mass spectrometry to investigate protein compositions of the AH obtained from individual human cataract eyes from 10 patients with iERM and 10 age-matched controls without iERM. Eight proteins were differentially expressed between the iERM and control samples, among which six proteins were upregulated and two were downregulated. A gene ontology (GO) analysis revealed that iERM was closely associated with several biological processes, such as immunity interactions, cell proliferation, and extracellular matrix remodeling. Additionally, multiple proteins, including lumican, cyclin-dependent kinase 13, and collagen alpha-3(VI) chain, were correlated with the central retinal thickness, indicating a multifactorial response in the pathogenic process of iERM. Changes in the AH level of lumican between iERM and control samples were also confirmed by an enzyme-linked immunosorbent assay. In conclusion, several pathological pathways involved in iERM were identified in the AH by a proteomic analysis, including immune reactions, cell proliferation, and remodeling of the extracellular matrix. Lumican is a potential aqueous biomarker for predicting iERM development and monitoring its progression. More clinical parameters also need to be identified to complete the analysis, and those could provide additional targets for treating and preventing iERM.
| S-EPMC9106516 | biostudies-literature
Project description:PurposeTo describe longitudinal retinal fluid dynamics on spectral domain OCT and to identify imaging biomarkers that predict the worsening of DME with interval extension during anti-vascular endothelial growth factor (VEGF) therapy.DesignA post hoc sub-analysis of phase III, VISTA-DME study.MethodsEyes received either intravitreal aflibercept injection 2 mg every 4 weeks (2q4) or every 8 weeks after 5 initial monthly injections (2q8), and eyes imaged with the Cirrus HD-OCT system were included. The macular cube was analyzed for 10 time-points from baseline through week 100. Retinal OCT images were evaluated using a novel software platform to extract retinal fluid features for calculation of volumetric fluid parameters, including the retinal fluid index (RFI): the percentage of retinal volume that was occupied by intraretinal fluid.ResultsFifty-five eyes were included in the 2q4 group, and 58 eyes were included in the 2q8 group. Early RFI volatility with a central macular RFI increase by ≥5 points from week 4 to 8 (P = .004, odds ratio [OR] 31.3, 95% confidence interval [CI] 3.0 to 329) and cumulative RFI volatility with an aggregate increase in macular RFI by ≥10 points from those timepoints with increased RFI between baseline to week 20, P = .005, OR 10.2, 95% CI 2.1 to 51.3) were both significant predictors for the worsening of DME and visual acuity when the treatment interval was extended to 8 weeks in the 2q8 group.ConclusionsEarly fluid dynamics as measured by (1) early RFI volatility and (2) cumulative RFI instability with aggregate increased RFI were associated with intolerance of interval extension.
| S-EPMC9307417 | biostudies-literature
Project description:PurposeTo assess the influence of time interval since last injection and time from baseline on central retinal thickness (CRT) in neovascular age-related macular degeneration (nAMD) with fluid refractory to monthly anti-VEGF treatment.MethodsThis retrospective study included nAMD eyes with incomplete response to anti-VEGF defined by the presence of intra- or subretinal fluid on optical coherence tomography despite maximal (monthly) anti-VEGF dosing. The outcome measure was CRT, and two time variables (time from last injection ant time from baseline) were the independent factors included in the individual correlation analyses. In addition, an association analysis was performed.ResultsSixty eyes of 56 patients (67.9% females, mean age: 78.7 ± 6.8 years) were included with a mean included time period of 35.6 months. A significant positive correlation between CRT and the time from last injection occurred in 24 (40%) and 25 (42%) eyes by univariate and multivariate analysis, respectively. Time from baseline was significantly correlated with CRT in 29 (48.3%) and 30 (50%) eyes by univariate and multivariate analysis, respectively. This correlation was positive in 12 (20%) and negative in 18 eyes (30%). No association with such correlation was found.ConclusionSo-called refractory nAMD frequently shows a correlation of CRT with the interval in days from the preceding anti-VEGF injection, revealing that there is a subgroup of short-term responsiveness of the residual fluid. Moreover, slower CRT changes may occur over the years, either decrease or increase. In case of a slow CRT increase, this might require a diagnostic workup and therapeutic change.
| S-EPMC8166689 | biostudies-literature
Project description:PurposeThe bradykinin 1 receptor may be important in inflammatory retinal vascular leakage in diabetic macular edema. BI 1026706 is an antagonist of bradykinin 1 receptor that has demonstrated efficacy in preclinical studies. Boehringer Ingelheim trial 1320.22 (NCT02732951) was a randomized, double-blind, placebo-controlled study. The pharmacodynamics, safety, and tolerability of oral BI 1026706 for 12 weeks were evaluated in patients with type 1 or type 2 diabetes mellitus and mild visual impairment owing to center-involved diabetic macular edema.MethodsPatients (n = 105) were randomized to receive either oral BI 1026706 100 mg twice daily (morning and evening) or placebo for 12 weeks. The primary end point of the study was week 12 change from baseline in central subfield foveal thickness (CSFT) by spectral domain optical coherence tomography. Additional end points included absolute CSFT values, safety, and pharmacokinetics.ResultsAfter 12 weeks of treatment, there was no meaningful change from baseline in the adjusted mean CSFT in either treatment group (BI 1026706, 10.3 µm; placebo, -6.2 µm; adjusted mean treatment difference, 16.5 µm [95% confidence interval, -16.2 to 49.1]). There were also no differences in best-corrected visual acuity outcomes between treatment groups. Most reported adverse events were of mild or moderate intensity, and were balanced between treatment groups.ConclusionsBI 1026706 was not superior to placebo in CSFT week-12 change from baseline. Therefore, BI 1026706 does not reduce CSFT, a morphologic sign of diabetic macular edema.Translational relevanceKinin-kallikrein inhibition effects may not be apparent over 12 weeks for bradykinin 1 receptor inhibition alone.
| S-EPMC7396196 | biostudies-literature